PARACYCLOPHANE-BASED LIGANDS, THEIR PREPARATION AND USE IN CATALYSIS

Description

[0001] This invention relates to ligands used in transition metal-catalysed reactions and in particular to substituted paracyclophanes.

[0002] Rozenberg et al (Tetrahedron Letters 44 (2003) 3801-3804) describes planar chiral bidentate [2.2]paracyclophane ligands.

[0003] Paracyclophanes and in particular [2.2]-paracyclophane derivatives are established ligands for transition metal-catalysed asymmetric reactions (see for example, S. E. Gibson and J. D. Knight, Org. Biomol. Chem., 2003, 1, 1256-1269). Of these, paracyclophane bis(phosphines) have attracted considerable attention because catalysts derived from them show high levels of activity and selectivity in a number of useful asymmetric transformations.

[0004] For example, WO 97/47632 describes paracyclophane bis(phosphine) ligands and rhodium (Rh), ruthenium (Ru), iridium (Ir) or palladium (Pd) catalysts derived therefrom for asymmetric hydrogenation, isomerization, hydroboration, cyclization, arylation, alkylation and amination reactions. The ligands described have the formula depicted below;

[0005] Where both X groups are the identical, these ligands posses C₂ symmetry, that is they are chiral and have a C₂ axis of symmetry. For example, the C₂-symmetric [2.2] ligand where X = - (CH₂CH₂)-, known as PHANEPHOS, may be used in the asymmetric hydrogenation of ketones when comprising part of a Ru-diamine complex (see WO 01/74829).

[0006] WO 02/057278 describes paracyclophane ligands structurally related to the paracyclophane bis(phosphines) where the phenyl groups bound to the phosphorus in the [2.2]paracyclophane structure are replaced by oxygen, nitrogen, chloride or hydrogen atoms. These ligands are depicted below;

[0007] Rh, Ir and Ru catalysts derived therefrom were used in asymmetric hydrogenation reactions.

[0008] WO 2004/111065 describes substituted paracyclophanes of formula (I)

wherein X¹ and X² are linking groups comprising between 2 to 4 carbon atoms, Y¹ and Y² are selected from the group consisting of hydrogen, halide, oxygen, nitrogen, alkyl, cycloalkyl , aryl or heteroaryl, Z¹, Z² and Z³ are substituting groups that optionally contain functional groups, a, b, c, d, e and f are 0 or 1 and a + b + c + d +e + f = 1 to 6. Preferably X¹ and X² are -(C₂H₄)- and a + b + c + d + e + f = 1 or 2.

[0009] Whereas the paracyclophane ligands described are effective for many asymmetric transformations there is still a need to improve the activity and selectivity of catalysts derived from them over a broader range of reactions and substrates.

[0010] The above ligands rely on the dual functionality provided by the two phosphorus atoms to provide the desired selectivity. We have found surprisingly that certain paracyclophanes comprising only one phosphorus moiety are useful ligands.

[0011] Accordingly, the present invention provides a substituted paracyclophane as defined in claim 5, a substituted bromoparacyclophane as defined in claim 11 and a metal complex as defined in claims 16-19.

[0012] The present invention also provides a substituted paracyclophane of formula (I)

wherein X¹ and X² are linear, branched or cyclic linking groups wherein the link is formed from 2, 3 or 4 carbon atoms, and wherein the link may optionally contain in addition to the carbon atoms a heteroatom selected from the group consisting of O, N or S, and wherein the carbon atoms in the linking group may optionally be substituted with a halide,
Y¹ and Y² are selected from the group consisting of hydrogen, halide, straight chain C1-C20 alkyl, branched chain C1-C20 alkyl, cycloalkyl , aryl or heteroaryl and Z is an unsubstituted linear, branched or cyclic alkyl group, substituted or unsubstituted aryl group or substituted or unsubstituted heteroaryl, group,
wherein, when Z is a substituted aryl group, Z is a 2,5-disubstituted phenyl group, wherein the substituents are selected from one or more of halide, hydroxyl, C1-10 alkoxy, CHO, CO₂H, CN, NH₂, NHR or NR₂ where R is C1-10 alkyl or aryl; and
wherein, when Z is a substituted heteroaryl group, the substituents are selected from one or more of halide, hydroxyl, C1-30 alkoxy, carboxyl, methacryl, vinyl, nitrile, nitro, sulphate, mercapto or amino.

[0013] Linking groups X¹ and X² provide links between the benzene rings of the paracyclophane structure that comprise between 2 and 4 carbon atoms. Hence X¹ and X² are linear, branched or cyclic structures where the link is formed via 2, 3 or 4 carbon atoms. The links may, in addition to the carbon atoms, contain heteroatoms such as O, N or S (where the N atom may in turn be bonded to an alkyl group such as CH₃, C₂H₅, C₃H₇ or C₄H₉ or an aryl group, and the S atom may be bonded to an alkyl or aryl group or be part of an SO or SO₂ moiety) and/or the carbon atoms in the linking group may be substituted with a halide, e.g. one or more fluorine atoms. Hence linking groups X¹ and X² may independently be for example -(CH₂)_2-4-,-CH₂OCH₂-, -CH₂N(CH₃)CH₂-, -CH₂SO₂CH₂-, -C₂F₄- or ortho, meta or para -C₆H₄ Such modification of the linking group may be useful for adapting the substituted paracyclophane to different reaction conditions, e.g. solvents. Preferably the linking groups comprise -(C₂H₄)-,-(Q₃H₆)- or -(C₄H₈)-. More preferably X¹ and X² are the same and most preferably X¹ and X² are both -(C₂H₄)-.

[0014] In one embodiment the paracyclophane is a mono(phosphine) where Y¹ and Y² may independently be hydrogen, halide (Cl, Br, F or I) or straight chain or branched alkyl groups (e.g. C1-C20) such as methyl, ethyl, propyl, iso-propyl, butyl, iso-butyl, sec-butyl, tert-butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, dodecyl, and stearyl, cycloalkyl groups (e.g. C3-C10) such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or adamantyl, or aryl groups such as phenyl, naphthyl or anthracyl. The alkyl groups may be optionally substituted with one or more substituents such as halide (Cl, Br, F or I) or alkoxy groups, e.g. methoxy, ethoxy or propoxy groups. The aryl groups may be optionally substituted with one or more substituents such as halide (Cl, Br, F or I), methyl, trifluoromethyl or methoxy groups. Suitable substituted aryl groups include 4-methylphenyl, 3,5-dimethylphenyl, 4-methoxyphenyl and 4-methoxy-3,5-dimethylphenyl. Substituted or unsubstituted heteroaryl groups such as pyridyl may also be used. In an alternative embodiment, Y¹ and Y² on each phosphorus atom may be linked so as to form a ring structure incorporating the phosphorus atom. In such an embodiment, preferably Y¹ and Y² are linked so as to provide each phosphorus atom in a 4- to 7-membered ring. Preferably, Y¹ and Y² are the same and are cyclohexyl, phenyl or substituted phenyl groups.

[0015] In formula (I), Z is an unsubstituted linear, branched or cyclic alkyl group, substituted or unsubstituted aryl group or substituted or unsubstituted heteroaryl group. The unsubstituted alkyl group may be an unsubstituted C1-C30, preferably an unsubstituted C1-C10 alkyl group, which may be cyclic, branched or linear, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, sec-butyl, tert-butyl, n-pentyl, hexyl, cyclohexyl, n-octyl, iso-octyl, 2-ethylhexyl, n-nonyl, iso-decyl, undecyl or octadecyl. The unsubstituted aryl group Z may be an unsubstituted phenyl, naphthyl or anthracyl group. The substituted or unsubstituted heteroaryl group may be a substituted or unsubstituted furan, thiophen, morpholine, pyrrole, pyridine or quinoline group.

[0016] Substituting groups may be one or more of halide (e.g. F, Cl, Br, I), hydroxyl, C1-30 alkoxy, carbonyl, carboxyl, methacryl., vinyl, nitrile, nitro, sulphate, mercapto and amino.

[0017] When Z is a substituted aryl group, Z is a 2,5-disubstituted phenyl group having one or more substituting groups selected from halide (e.g. F, Cl, Br, I), hydroxyl, C1-C10 alkoxy, carbonyl (CHO), carboxyl (CO₂H), nitrile (CN), amino (NH₂) and amine (NHR or NR₂) where R is C1-10 alkyl or aryl. Alkoxy groups, e.g. methoxy groups, are particularly preferred. The substituting groups on Z may be the same or different. In a particularly preferred embodiment Z is a 2,5-dimethoxy phenyl group.

[0018] The substituted paracyclophane of the present invention may be prepared by substitution reactions on a suitable paracyclophane intermediate. In particular, we have found that substituted pseudo-ortho dibromo-paracyclophane provides a very useful starting point for the synthesis of the substituted paracyclophane of the present invention.

[0019] Accordingly, the present invention further provides a method for preparation of a substituted paracyclophane of formula (I), by

(a) performing a substitution reaction on a pseudo-ortho dibromoparacyclophane to form an intermediate substituted bromoparacyclophane of formula (II), and

(b) reacting the substituted bromoparacyclophane of formula (II) with a phosphorus compound comprising P(Y¹Y²), wherein X¹ and X² are linear, branched or cyclic linking groups wherein the link is form via 2, 3 or 4 carbon atoms, and wherein the link may optionally contain in addition to the carbon atoms a heteroatom selected from the group consisting of O, N or S, and wherein the carbon atoms in the linking group may optionally be substituted with a halide,
Y¹ and Y² are selected from the group consisting of hydrogen, halide, straight chain C1-C20 alkyl, branched chain C1-C20 alkyl, cycloalkyl, aryl or heteroaryl, and Z is a substituted or unsubstituted linear, branched or cyclic alkyl group, substituted or unsubstituted aryl group or substituted or unsubstituted heteroaryl group,
wherein, when Z is a substituted aryl group, Z is a 2,5-disubstituted phenyl group, wherein the substituents are selected from one or more of halide, hydroxyl, C1-10 alkoxy, CHO, CO₂H, CN, NH₂, NHR or NR₂ where R is C1-10 alkyl or aryl; and
wherein, when Z is a substituted alkyl or substituted heteroaryl group, the substituents are selected from one or more of halide, hydroxyl, C1-30 alkoxy, carboxyl, methacryl, vinyl, nitrile, nitro, sulphate, mercapto or amino.

[0020] Accordingly, the invention further provides a substituted bromoparacyclophane of formula (II)

wherein X¹ and X² are linear, branched or cyclic linking groups wherein the link is formed via 2, 3 or 4 carbon atoms, and wherein the link may optionally contain in addition to the carbon atoms a heteroatom selected from the group consisting of O, N or S, and wherein the carbon atoms In the linking group may optionally be substituted with a halide, and wherein:

a) Z is a substituted or unsubstituted linear, branched or cyclic alkyl group, unsubstituted aryl group or substituted or unsubstituted heteroaryl group,
wherein, when Z is a substituted alkyl or substituted heteroaryl group, the substituents are selected from one or more of halide, hydroxyl, C1-30 alkoxy, carboxyl, methacryl, vinyl, nitrile, nitro, sulphate, mercapto or amino; or

b) Z is a 2,5-disubstituted phenyl group, wherein the substituents are selected from one or more of halide, hydroxyl, C1-10 alkoxy, CHO. CO₂H, CN, NH₂, NHR or NR₂ where R is C1-10 alkyl or aryl.

[0021] The pseudo-ortho dibromoparacyclophane from which the substituted bromoparacyclophane (II) is synthesised may be prepared according to known methods. Typically a paracyclophane may be reacted with bromine in the presence of iron in a suitable solvent (see D. J. Cram et al, J. Am. Chem. Soc., 1969, 91, (13), 3527). In particular, for commercially available [2.2] paracyclophane, the synthesis of the pseudo-ortho dibromo[2.2]paracyclophane may be performed according to the methods described in example 1 and example 2 on pages 31 and 32 of aforesaid WO 97/47632.

[0022] Preferably the substitution reaction is performed using a boronic acid, of formula Z-B(OH)₂, in which Z may be substituted or unsubstituted. This reaction, which is analogous to a Suzuki C-C coupling reaction, may be performed using a palladium catalyst in the presence of potassium phosphate in a suitable solvent at reflux under nitrogen. This reaction is depicted below;

[0023] Surprisingly the mono-substituted product forms in high yield.

[0024] Once the substituted bromoparacyclophane (II) has been synthesised, the next step of the method of the present invention is the conversion of the remaining pseudo-ortho bromide group to the desired phosphine, phosphonite, phosphorus amide or phosphonamidite by reacting the substituted bromoparacyclophane (II) with a phosphorus compound comprising P(Y¹Y²). This reaction may be performed according to a number of known methods. Preferably, substituted paracyclophane mono(phosphines) are prepared by treating the substituted bromoparacyclophane of formula (II) with an alkyl lithium reagent, e.g. tert-Butyl Lithium (tBuLi) in a suitable solvent at low temperature and the anion quenched with an aryl-, alkyl, or cycloalkyl-phosphinylchloride, e.g. dicyclohexylphosphinylchloride (Cy₂PCl) to give the desired substituted paracyclophane mono(phosphine). A similar method may be used for other aryl and alkyl phosphines. An example of this reaction is depicted as follows;

[0025] Alternatively, the more air and moisture-stable corresponding phosphine oxide may be prepared using Ph₂POCl and the phosphine oxide subsequently reduced using e.g. HSiCl₃.

[0026] Methods suitable for preparing a phosphonite, phosphorus amide and phosphonamidite from the substituted bromoparacyclophane of formula (II) may be found in A. Zanotti-Gerosa et al, Org. Lett., 2001, 3687. For example, a substituted bromoparacyclophane may be converted to the corresponding substituted paracyclophane mono(phosphonite) in an analogous manner to the phosphine by direct metallation of the substituted bromoparacyclophane (II) with a strong organometallic base and reaction with the appropriate chloro-phosphonite. The substituted paracyclophane mono(phosphonite) may be synthesised by treatment of a substituted paracyclophane mono(dichlorophosphine) or substituted paracyclophane phosphorus-diamide with an alcohol, diol or metal diolate. The substituted paracyclophane mono(dichlorophosphine) may itself be obtained via the paracyclophane phosphorus diamide which may be prepared by direct metallation of the substituted bromoparacyclophane (II) with a strong organometallic base and reaction with a chloro-phosphorus-diamide such as Cl-P(NCH₃)₂ or ClP(iso-C₃H₇). The resulting paracyclophane phosphorus-diamide may be converted to the paracyclophane mono(dichlorophosphine) by treatment with an HCl solution.

[0027] The substituted paracyclophane of the present invention is chiral and may adopt one of two enantiomeric forms i.e. an (R)- or (S)-configuration. Accordingly, the paracyclophane may comprise a racemic mixture of enantiomers. Alternatively and preferably the substituted paracyclophane comprises a substantially enantiomerically-pure enantiomer (i.e having an enantiomeric excess >75%, preferably >95%). To obtain a substantially pure enantiomer the substituted paracyclophane may be prepared from a substantially enantiomerically-pure pseudo-ortho dibromoparacyclophane starting material. For example, resolution of a racemic mixture of pseudo-ortho dibromoparacyclophane may be effected on a chiral stationary phase such as crystalline cellulose triacetate using ethanol as eluant or on chiral HPLC columns. Alternatively, a chiral resolution may be performed at later stages during the synthetic process. For example, the resolution may be performed on the substituted paracyclophane mono(phosphine), phosphine oxide, phosphonite, phosphorus amide or phosphonamidite (I) using known crystallisation techniques or separation on chiral chromatography columns.

[0028] It will be understood by those skilled in the art that where one enantiomer of a substituted paracyclophane is depicted, the other is included within the scope of the present invention.

[0029] The substituted paracyclophane (I) of the present invention may be used as a ligand to prepare metal complexes suitable for use as catalysts in chemical reactions.

[0030] Accordingly, the invention further provides a metal complex comprising the reaction product of a metal compound and a substituted paracyclophane of formula (I)

wherein X¹ and X² are linear, branched or cyclic linking groups wherein the link is formed via 2, 3 or 4 carbon atoms, and wherein the link may optionally contain in addition to the carbon atoms a heteroatom selected from the group consisting of O, N or S, and wherein the carbon atoms in the linking group may optionally be substituted with a halide,
Y¹ and Y² are selected from the group consisting of hydrogen, halide, straight chain C1-C20 alkyl, branched chain C1-C20 alkyl, cycloalkyl, aryl or heteroaryl, and Z is an unsubstituted linear, branched or cyclic alkyl group, substituted or unsubstituted aryl group or substituted or unsubstituted heteroaryl group,
wherein, when Z is a substituted aryl group, Z is a 2,5-disubstituted phenyl group, wherein the substituents are selected from one or more of halide, hydroxyl, C1-10 alkoxy, CHO, CO₂H, CN, NH₂, NHR or NR₂ where R is C1-10 alkyl or aryl; and
wherein, when Z is a substituted heteroaryl group, the substituents are selected from one or more of halide, hydroxyl, C1-30 alkoxy, carboxyl, methacryl, vinyl, nitrile, nitro, sulphate, mercapto or amino.

[0031] The substituted paracyclophane (I) may be combined with the metal compound in a racemic mixture or in a substantially enantiomerically pure form. Preferably the substituted paracyclophane (I) is substantially enantiomerically-pure (i.e having an enantiomeric excess >75%, preferably >95%). The metal compound may be any metal compound that is able to react with the substituted paracyclophane (I) to provide a metal complex. The metal compound is preferably a compound of palladium (Pd), platinum (Pt), rhodium (Rh), iridium (Ir) or ruthenium (Ru), which may be a metal salt, e.g. halide, carboxylate, sulphonate or phosphonate, or an organometallic compound. The metal complex may additionally comprise ligands that are able to reversibly co-ordinate. Reversibly co-ordinating ligands may improve the stability of the metal complexes and may be provided during the synthesis of the metal complex or may react with the metal complex when it is added to the reaction mixture. By "reversibly co-ordinating" we mean a ligand that can be readily displaced by other molecules in a reaction mixture. Such reversibly co-ordinating ligands may be selected from the list comprising dienes, particularly cyclic dienes such as cyclooctadiene or norbornadiene, C1-C4 alcohols, ethers, cyclic ethers, diols, e.g. 1,2-diols and C2 or C3 olefins, e.g. ethylene. In addition, the metal complex may additionally comprise a non-reversibly co-ordinating ligand that may be used to modify the reactivity and selectivity of the metal complex catalyst. Non-reversibly co-ordinating ligands that may be used are diamines, for example 1,2-diphenylethylenediamine, 1,2-cyclohexylethylenediamine and ethylene diamine and particularly substantially enantiomerically-pure chiral 1,2-diamines such as (S,S)-1,2-diphenylethylenediamine.

[0032] To satisfy the oxidation state of the metal complex, it may when the oxidation state of the metal requires, further comprise a counter-ion. The counter-ion may be any suitable anion but is preferably a non-nucleophile anion selected from trifluoromethanesulphonate (triflate or OTf), perchlorate (ClO₄), hexafluoroantimonate (SbF₆) or hexafluorophosphate (PF₆).

[0033] The metal complexes may be readily prepared from the substituted paracyclophane of the present invention. In general, the metal compound is combined with the substituted paracyclophane and optionally the reversibly co-ordinating ligand and/or non-reversibly co-ordinating ligand in a suitable solvent and heated if necessary to form the desired metal complex.

[0034] The substituted paracyclophane ligands of the present Invention may be racemic or chiral, and when chiral, are able to produce chiral metal complex catalysts. The chiral metal complex catalysts of the present invention may be applied to a large number of reactions used to produce chiral or non-chiral products. Such reactions include but are not limited to asymmetric hydrogenation reactions such as the chiral hydrogenation of enamide and non-enamide structures, asymmetric hydrogenation in iso-quinoline synthesis, the asymmetric hydrogenation of unsaturated alcohols, and the asymmetric hydrogenation of ketones and mines.

[0035] The catalysts of the present invention may also be used for carbon-carbon coupling reactions such as the Heck or Suzuki reactions, for the enantioselective isomerization of olefins, asymmetric hydroboration reactions, asymmetric cyclisation of olefinic aldehydes, asymmetric arylation and alkylation reactions and the amination of aryl halides (Hartwig-Buchwald reaction).

[0036] Where appropriate, to achieve high levels of enantiomeric purity in a reaction it Is preferred that the metal complex comprises a substantially enantiomerically-pure substituted paracyclophane (I).

[0037] The conditions for using the metal complex catalysts are typically similar to those used for structurally related catalysts. The metal complex may be formed as a catalyst in situ, or separately synthesised.

[0038] While we have found the metal complexes comprising substituted paracyclophanes of the present invention to be effective homogeneous catalysts it may be desirable to provide such metal complexes on solid supports as heterogeneous catalysts. Heterogeneous catalysts have the advantages that they are often easier to separate from the reaction mixtures and may in some circumstances be recycled. To form a heterogeneous catalyst, the metal complex may be absorbed or ion-exchanged into a suitable solid support material, e.g. a zeolite. Alternatively the metal complex may be reacted with functional groups present on a solid support material to form a covalently bound catalyst. The solid support materials to which the substituted paracyclophane may be attached, may be polymers, metal oxides or sol-gel materials that have sites capable of reacting with the metal complex.

[0039] The invention is further illustrated by reference to the following examples where
dppf = 1,1'-bis(diphenylphosphino)ferrocene,
dba = dibenzylideneacetone,
Cy = cyclohexyl, and
and room temperature = 20-25°C unless otherwise stated.

[0040] The nomenclature of the substituted paracyclophanes was assigned as in: S. Gisbon metal. Organic and Biomolecular Chemistry 2003, 1256.

Example 1. Synthesis of a monophosphine ligand:

(a) preparation of a substituted bromoparacyclophane

[0041] 

[0042] To a Schlenk tube were added (rac)-4,12-dibromoparacyclophane 1.83g (5.0 mmol), 2,6-dimethoxyphenylboronic acid 1.37g (7.5 mmol, 1.5 equiv), Pd(dppf)Cl₂ 164mg (0.20 mmol, 4 mol %), and K₃PO₄ 2.12g (10.0 mmol, 2.0 equiv). The flask was evacuated and backfilled with nitrogen three times. Fresh distilled toluene (20 mL) was introduced, and the flask was sealed, stirred at reflux for 24 h. The reaction mixture was cooled, diluted with toluene (30 mL), and hydrolyzed with 10 % NaOH (30 mL). Separated and extracted the water phase with EtOAc (3 x 25 mL). The organic layers were dried over MgSO₄ and concentrated under reduced pressure. The residue was purified by column chromatography (EtOAc/hexane, 30:1) on silica gel to afford white solid products 1.82g (86 % yields). ¹H NMR (400 MHz, CDCl₃) δ 7.24 (t, J = 8.4 Hz, 1H), 7.10 (s, 1H), 7.75 (d, J = 8.4 Hz, 1H), 6.73 (s, 1H), 6.67 (s, 2H), 6.54 - 6.51 (m, 2H), 6.39 (d, J = 7.6 Hz, 1H), 4.10 (s, 3H), 3.60 - 3.51 (m, 1H), 3.48 (s, 3H), 3.22 - 3.10 (m, 2H), 2.95 - 2.75 (m, 4H), 2.65 - 2.55 (m, 1 H); ¹³C NMR (100 MHz, CDCl₃) δ 158.6, 158.5, 141.5, 140.8, 139.7, 137.4, 137.1, 134.6, 133.5, 133.0, 131.6, 131.2, 129.8, 129.0, 126.9, 118.5, 105.1, 105.0, 56.5, 55.8, 37.3, 34.9, 34.8, 32.9; MS m/z 442: 440 = 1:1 (M+NH₃, 100), 425: 423 = 1:1 (M+H, 72).

(b) conversion to the monophosphine

[0043] 

[0044] An oven-dried Schlenk flask was charged with 4-bromo-12-(2',6'-dimethoxy)phenyl-paracyclophane 1.06g (2.5 mmol), evacuated and backfilled with nitrogen three times, then 50 mL fresh distilled Et₂O was introduced. After cooled to -78 °C, 1.3 mL (3.25 mmol, 2.5 M in hexane) n-BuLi was dropwise added. Stirred at -78 °C for 2h, and gradually warmed to room temperature for another 3h. 0.66 mL (3 mmol) ClPCy₂ was added, the reaction mixture was stirred at room temperature overnight. Added 0.5 mL 1M NaOH and stirred for 10 min, removed the solvent. The crude product was purified by flash column chromatography (hexane) on silica gel, and 0.89 g (66 % yields) white solid products obtained. ¹H NMR (400 MHz, CDCl₃) δ 7.19 (t, J = 8.4 Hz, 1 H), 6.77 - 6.66 (m, 4H), 6:51 - 6.46 (m, 3H), 6.43 (s, 1H), 4.05 (s, 3H), 4.05 - 4.01 (m, 1 H), 3.37 (s, 3H), 3.25 - 2.88 (m, 6H), 2.85 - 2.77 (m, 1 H), 2.08 - 2.03 (m, 1H), 1.98 - 1.93 (m, 1 H), 1.80 - 1.63 (m, 6H), 1.48 - 1.43 (m, 3H), 1.30 - 0.73 (m, 11 H); ¹³C NMR (100 MHz, CDCl₃) δ 159.4, 157.7, 146.7, 146.5, 138.2, 137.4, 135.0, 134.8, 134.6, 134.5, 133.8, 133.4, 133.3, 130.7, 128.4, 118.5, 105.1, 104.0, 56.5, 55.2, 37.3, 37.1, 34.9, 34.8, 34.2, 32.0, 30.9, 29.1, 28.7, 28.2, 27.6, 27.5, 27.2, 26.7; ³¹P NMR (162 MHz, CDCl₃) δ -1.72; MS m/z 541 (M+H, 100); Anal. Calcd for C₃₆H₄₅O₂P: C, 79.97; H, 8.39. Found: C, 79.97; H, 8.44.

Example 2. Catalysis

(a) Amination of Aryl Chlorides (Buchwald-Hartwig C-N coupling reaction).

[0045] An oven-dried carousel reaction tube was loaded with 4.6mg Pd₂(dba)₃ (0.005 mmol, 0.5 mol%), 10.8mg ligand of Example 1 (0.02 mmol, 2 mol%), and 135mg NaOtBu (1.4 mmol, 1.4 equiv), then evacuated and backfilled with nitrogen three times. Fresh distilled dioxane (4 mL), aryl chloride (1 mmol), and amine (1.2 mmol) were added successively. The tube was sealed, and the reaction mixture was stirred at 100 °C for the mentioned time. After the mixture was cooled to room temperature, 15 mL of EtOAc was added and the mixture was washed with 5 mL of brine. The organic layer was dried over MgSO₄ and concentrated under reduced pressure. The crude product was purified by flash column chromatography on basic Al₂O₃.

Entry	ArCl	Amine	Product	Time / h	Yield / %
1				2	95
2				3	94
3				3	88
4				2	97
5				3	85
6				3	65
7				6	60
8				5	91
9				3	93
10				3	90
11				5	89
12				5	81
13				5	93

(b) Suzuki Coupling of Aryl Chlorides.

[0046] An oven-dried carousel reaction tube was charged with boronic acid (1.5 mmol), K₃PO₄ (637 mg, 3 mmol), and ligand of Example 1 (1.1 mg, 0.002mmol, 0.2 mol%). The reaction vessel was evacuated and backfilled with nitrogen. This process was repeated five times. Through a rubber septum, aryl chloride (1 mmol), 0.5 mL Pd(OAc)₂ solution (2 x 10^-3 M in dioxane, 0.001 mmol, 0.1 mol%), and fresh distilled dioxane (4.5 mL) were introduced. The tube was sealed, and the reaction mixture was stirred at 80 °C for 12h. After the mixture was cooled to room temperature, 15 mL of EtOAc was added and the mixture was washed with 5 mL of brine. The organic layer was dried over MgSO₄ and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel.

Entry	ArCl	ArB(OH)2	Product	Yield / %
1				90
2				87
3				90
4				96
5				92
6				90
7				95
8				97
9				93
10a				86
11a				84
12b				94

a. 0.2 mol% Pd(OAc)2 and 0.4 mol% L used; b. 0.6 mol% Pd(OAc)2 and 1.2 mol% L used.

Claims

1. A substituted paracyclophane of formula (I)

wherein X¹ and X² are linear, branched or cyclic linking groups wherein the link is formed via 2, 3 or 4 carbon atoms, and wherein the link may optionally contain in addition to the carbon atoms a heteroatom selected from the group consisting of O, N or S, where the N atom may in turn be bonded to an alkyl group such as CH₃, C₂H₅, C₃H₇ or C₄H₉ or an aryl group, and the S atom may be bonded to an alkyl or aryl group or be part of an SO or SO₂ moiety, and wherein the carbon atoms in the linking group may optionally be substituted with a halide,
Y¹ and Y² are selected from the group consisting of hydrogen, halide, straight chain C1-C20 alkyl, branched chain C1-C20 alkyl, cycloalkyl, aryl or heteroaryl and Z is an unsubstituted linear, branched or cyclic alkyl group, substituted or unsubstituted aryl group or substituted or unsubstituted heteroaryl group,
wherein, when Z is a substituted aryl group, Z is a 2,5-disubstituted phenyl group, wherein the substituents are selected from one or more of halide, hydroxyl, C1-10 alkoxy, CHO, CO₂H, CN, NH₂, NHR or NR₂ where R is C1-10 alkyl or aryl; and
wherein, when Z is a substituted heteroaryl group, the substituents are selected from one or more of halide, hydroxyl, C1-30 alkoxy, carboxyl, methacryl, vinyl, nitrile, nitro, sulphate, mercapto or amino.

2. A substituted paracyclophane according to claim 1 wherein X¹ and X² are both -C₂H₄-.

3. A substituted paracyclophane according to claim 1 or claim 2 wherein Z is an unsubstituted phenyl, naphthyl or anthracyl group.

4. A substituted paracyclophane according to claim 1 or claim 2 wherein Z is a 2,5-disubstituted phenyl group.

5. A substituted paracyclophane which is:

6. A method for preparation of a substituted paracyclophane of formula (I) by,

(a) performing a substitution reaction on a pseudo-ortho dibromoparacyclophane to form an intermediate substituted bromoparacyclophane of formula (II), and

(b) reacting the substituted bromoparacyclophane with a phosphorus compound comprising P(Y¹Y²),
wherein X¹ and X² are linear, branched or cyclic linking groups wherein the link is formed via 2, 3 or 4 carbon atoms, and wherein the link may optionally contain irraddition to the carbon atoms a heteroatom selected from the group consisting of O, N or S, where the N atom may in turn be bonded to an alkyl group such as CH₃, C₂H₅, C₃H₇ or C₄H₉ or an aryl group, and the S atom may be bonded to an alkyl or aryl group or be part of an SO or SO₂ moiety, and wherein the carbon atoms in the linking group may optionally be substituted with a halide,
Y¹ and Y² are selected from the group consisting of hydrogen, halide, straight chain C1-C20 alkyl, branched chain C1-C20 alkyl, cycloalkyl, aryl or heteroaryl, and Z is a substituted or unsubstituted linear, branched or cyclic alkyl group, substituted or unsubstituted aryl group or substituted or unsubstituted heteroaryl group,
wherein, when Z is a substituted aryl group, Z is a 2,5-disubstituted phenyl group,
wherein the substituents are selected from one or more of halide, hydroxyl, C1-10 alkoxy, CHO, CO₂H CN, NH₂, NHR or NR₂ where R is C1-10 alkyl or aryl; and
wherein, when Z is a substituted alkyl or substituted heteroaryl group, the substituents are selected from one or more of halide, hydroxyl, C1-30 alkoxy, carboxyl, methacryl, vinyl, nitrile, nitro, sulphate, mercapto or amino.

7. A method according to claim 6 wherein the substitution reaction is performed using a boronic acid, of formula Z-B(OH)₂, in which Z may be substituted or unsubstituted.

8. A method according to claim 7 wherein the boronic acid comprises a 2,5-disubstituted phenyl group.

9. A substituted bromoparacyclophane of formula (II)

wherein X¹ and X² are linear, branched or cyclic linking groups wherein the link is formed via 2, 3 or 4 carbon atoms, and wherein the link may optionally contain in addition to the carbon atoms a heteroatom selected from the group consisting of O, N or S, where the N atom may in turn be bonded to an alkyl group such as CH₃, C₂H₅, C₃H₇ or C₄H₉ or an aryl group, and the S atom may be bonded to an alkyl or aryl group or be part of an SO or SO₂ moiety, and wherein the carbon atoms in the linking group may optionally be substituted with a halide, and wherein:

a) Z is a substituted or unsubstituted linear, branched or cyclic alkyl group, unsubstituted aryl group or substituted or unsubstituted heteroaryl group,
wherein, when Z is a substituted alkyl or substituted heteroaryl group, the substituents are selected from one or more of halide, hydroxyl, C1-30 alkoxy, carboxyl, methacryl, vinyl, nitrile, nitro, sulphate, mercapto or amino; or

b) Z is a 2,5-disubstituted phenyl group, wherein the substituents are selected from one or more of halide, hydroxyl, C1-10 alkoxy, CHO, CO₂H, CN, NH₂, NHR or NR₂ where R is C1-10 alkyl or aryl.

10. A substituted bromoparacyclophane according to claim 9 wherein Z is a 2,5-disubstituted phenyl group.

11. A substituted bromoparacyclophane which is:

12. A metal complex comprising the reaction product of a metal compound and a substituted paracyclophane of formula (I)

wherein X¹ and X² are linear, branched or cyclic linking groups wherein the link is formed via 2, 3 or 4 carbon atoms, and wherein the link may optionally contain in addition to the carbon atoms a heteroatom selected from the group consisting of O, N or S, where the N atom may in turn be bonded to an alkyl group such as CH₃, C₂H₅, C₃H₇ or C₄H₉ or an aryl group, and the S atom may be bonded to an alkyl or aryl group or be part of an SO or SO₂ moiety, and wherein the carbon atoms in the linking group may optionally be substituted with a halide,
Y¹ and Y² are selected from the group consisting of hydrogen, halide, straight chain C1-C20 alkyl, branched chain C1-C20 alkyl, cycloalkyl, aryl or heteroaryl, and Z is an unsubstituted linear, branched or cyclic alkyl group, substituted or unsubstituted aryl group or substituted or unsubstituted heteroaryl group,
wherein, when Z is a substituted aryl group, Z is a 2,5-disubstituted phenyl group, wherein the substituents are selected from one or more of halide, hydroxyl, C1-10 alkoxy, CHO, CO₂H, CN, NH₂, NHR or NR₂ where R is C1-10 alkyl or aryl; and
wherein, when Z is a substituted heteroaryl group, the substituents are selected from one or more of halide, hydroxyl, C1-30 alkoxy, carboxyl, methacryl, vinyl, nitrile, nitro, sulphate, mercapto or amino.

13. A metal complex according to claim 12 wherein the metal compound is a compound of palladium (Pd), platinum (Pt), rhodium (Rh), iridium (Ir) or ruthenium (Ru).

14. A metal complex according to claim 12 or claim 13 wherein the substituted paracyclophane (I) has an enantiomeric excess >75%.

15. A metal complex according to any one of claims 12 to 14 wherein the metal complex is supported on a solid support.

16. A metal complex comprising the reaction product of a metal compound and a substituted paracyclophane which is:

17. A metal complex according to claim 16 wherein the metal compound is a compound of palladium (Pd), platinum (Pt), rhodium (Rh), iridium (Ir) or ruthenium (Ru).

18. A metal complex according to claim 16 or claim 17 wherein the substituted paracyclophane (I) has an enantiomeric excess >75%.

19. A metal complex according to any one of claims 16 to 18 wherein the metal complexe is supported on a solid support.

20. The use of a metal complex according to any one of claims 13 to 15 and 17 to 19 as a catalyst in an asymmetric hydrogenation reaction.

21. The use of a metal complex according to any one of claims 13 to 15 and 17 to 19 as a catalyst for reactions selected from the list consisting of carbon-carbon coupling reactions, the enantioselective isomerization of olefins, asymmetric hydroboration reactions, asymmetric cyclisation of olefinic aidehydes, asymmetric arylation and alkylation reactions and the amination of aryl halides (Hartwig-Buchwald reaction).

Ansprüche

1. Substituiertes Paracyclophan der Formel (I)

wobei X¹ und X² für geradkettige, verzweigte oder cyclische Verknüpfungsgruppen stehen, wobei die Verknüpfung über 2, 3 oder 4 Kohlenstoffatome gebildet wird und wobei die Verknüpfung gegebenenfalls zusätzlich zu den Kohlenstoffatomen ein aus der aus 0, N und S bestehenden Gruppe ausgewähltes Heteroatom enthalten kann, wobei das N-Atom seinerseits an eine Alkylgruppe wie CH₃, C₂H₅, C₃H₇ oder C₄H₉ oder eine Arylgruppe gebunden sein kann und das S-Atom an eine Alkyl- oder Arylgruppe gebunden oder Teil einer SO- oder SO₂-Gruppierung sein kann, und wobei die Kohlenstoffatome in der Verknüpfungsgruppe gegebenenfalls durch ein Halogenid substituiert sein können, Y¹ und Y² aus der aus Wasserstoff, Halogenid, geradkettigem C1-C20-Alkyl, verzweigtem C1-C20-Alkyl, Cycloalkyl, Aryl und Heteroaryl bestehenden Gruppe ausgewählt sind und Z für eine unsubstituierte geradkettige, verzweigte oder zyklische Alkylgruppe, eine substituierte oder unsubstituierte Arylgruppe oder eine substituierte oder unsubstituierte Heteroarylgruppe steht, wobei, wenn Z für eine substituierte Arylgruppe steht, Z für eine 2,5-disubstituierte Phenylgruppe steht,
wobei die Substituenten aus einem oder mehreren von Halogenid, Hydroxyl, C1-10-Alkoxy, CHO, CO₂H, CN, NH₂, NHR und NR₂, wobei R für C1-10-Alkyl oder Aryl steht, ausgewählt sind; und
wobei, wenn Z für eine substituierte Heteroarylgruppe steht, die Substituenten aus einem oder mehreren von Halogenid, Hydroxyl, C1-30-Alkoxy, Carboxyl, Methacryl, Vinyl, Nitril, Nitro, Sulfat, Mercapto und Amino ausgewählt sind.

2. Substituiertes Paracyclophan nach Anspruch 1, wobei sowohl X¹ als auch X² für -C₂H₄- stehen.

3. Substituiertes Paracyclophan nach Anspruch 1 oder Anspruch 2, wobei Z für eine unsubstituierte Phenyl-, Naphthyl- oder Anthracylgruppe steht.

4. Substituiertes Paracyclophan nach Anspruch 1 oder Anspruch 2, wobei Z für eine 2,5-disubstituierte Phenylgruppe steht.

5. Substituiertes Paracyclophan, bei dem es sich um:

handelt.

6. Verfahren zur Herstellung eines substituierten Paracyclophans der Formel (I) durch

(a) Durchführen einer Substitutionsreaktion an einem Pseudo-ortho-dibromparazyklophan unter Bildung eines substituierten Bromparacyclophanzwischenprodukts der Formel (II) und

(b) die Umsetzung des substituierten Bromparacyclophans mit einer P(Y¹Y²) umfassenden Phosphorverbindung,
wobei X¹ und X² für geradkettige, verzweigte oder cyclische Verknüpfungsgruppen stehen, wobei die Verknüpfung über 2, 3 oder 4 Kohlenstoffatome gebildet wird und wobei die Verknüpfung gegebenenfalls zusätzlich zu den Kohlenstoffatomen ein aus der aus 0, N und S bestehenden Gruppe ausgewähltes Heteroatom enthalten kann, wobei das N-Atom seinerseits an eine Alkylgruppe wie CH₃, C₂H₅, C₃H₇ oder C₄H₉ oder eine Arylgruppe gebunden sein kann und das S-Atom an eine Alkyl- oder Arylgruppe gebunden oder Teil einer SO- oder SO₂-Gruppierung sein kann, und wobei die Kohlenstoffatome in der Verknüpfungsgruppe gegebenenfalls durch ein Halogenid substituiert sein können, Y¹ und Y² aus der aus Wasserstoff, Halogenid, geradkettigem C1-C20-Alkyl, verzweigtem C1-C20-Aklyl, Cycloalkyl, Aryl und Heteroaryl bestehenden Gruppe ausgewählt sind und Z für eine substituierte oder unsubstituierte geradkettige, verzweigte oder zyklische Alkylgruppe, eine substituierte oder unsubstituierte Arylgruppe oder eine substituierte oder unsubstituierte Heteroarylgruppe steht,
wobei, wenn Z für eine substituierte Arylgruppe steht, Z für eine 2,5-disubstituierte Phenylgruppe steht,
wobei die Substituenten aus einem oder mehreren von Halogenid, Hydroxyl, C1-10-Alkoxy, CHO, CO₂H, CN, NH₂, NHR und NR₂, wobei R für C1-10-Alkyl oder Aryl steht, ausgewählt sind; und
wobei, wenn Z für eine substituierte Alkyl- oder eine substituierte Heteroarylgruppe steht, die Substituenten aus einem oder mehreren von Halogenid, Hydroxyl, C1-30-Alkoxy, Carboxyl, Methacryl, Vinyl, Nitril, Nitro, Sulfat, Mercapto und Amino ausgewählt sind.

7. Verfahren nach Anspruch 6, wobei die Substitutionsreaktion unter Anwendung einer Boronsäure der Formel Z-B(OH)₂, in welcher Z substituiert oder unsubstituiert sein kann, durchgeführt wird.

8. Verfahren nach Anspruch 7, wobei die Boronsäure eine 2,5-disubstituierte Phenylgruppe umfasst.

9. Substituiertes Bromparacyclophan der Formel (II)

wobei X¹ und X² für geradkettige, verzweigte oder cyclische Verknüpfungsgruppen stehen, wobei die Verknüpfung über 2, 3 oder 4 Kohlenstoffatome gebildet wird und wobei die Verknüpfung gegebenenfalls zusätzlich zu den Kohlenstoffatomen ein aus der aus 0, N und S bestehenden Gruppe ausgewähltes Heteroatom enthalten kann, wobei das N-Atom seinerseits an eine Alkylgruppe wie CH₃, C₂H₅, C₃H₇ oder C₄H₉ oder eine Arylgruppe gebunden sein kann und das S-Atom an eine Alkyl- oder Arylgruppe gebunden oder Teil einer SO- oder SO₂-Gruppierung sein kann, und wobei die Kohlenstoffatome in der Verknüpfungsgruppe gegebenenfalls durch ein Halogenid substituiert sein können, und wobei:

a) Z für eine substituierte oder unsubstituierte geradkettige, verzweigte oder cyclische Alkylgruppe, unsubstituierte Arylgruppe oder substituierte oder unsubstituierte Heteroarylgruppe steht,
wobei, wenn Z für eine substituierte Alkyl- oder substituierte Heteroarylgruppe steht, die Substituenten aus einem oder mehreren von Halogenid, Hydroxyl, C1-30-Alkoxy, Carboxyl, Methacryl, Vinyl, Nitril, Nitro, Sulfat, Mercapto und Amino ausgewählt sind; oder

b) Z für eine 2,5-disubstituierte Phenylgruppe steht, wobei die Substituenten aus einem oder mehreren von Halogenid, Hydroxyl, C1-10-Alkoxy, CHO, CO₂H, CN, NH₂, NHR oder NR₂, wobei R für C1-10-Alkyl oder Aryl steht, ausgewählt sind.

10. Substituiertes Bromparacyclophan nach Anspruch 9, wobei Z für eine 2,5-disubstituierte Phenylgruppe steht.

11. Substituiertes Bromparacyclophan, bei dem es sich um:

handelt.

12. Metallkomplex, umfassend das Reaktionsprodukt einer Metallverbindung und eines substituierten Paracyclophans der Formel (I)

wobei X¹ und X² für geradkettige, verzweigte oder cyclische Verknüpfungsgruppen stehen, wobei die Verknüpfung über 2, 3 oder 4 Kohlenstoffatome gebildet wird und wobei die Verknüpfung gegebenenfalls zusätzlich zu den Kohlenstoffatomen ein aus der aus 0, N und S bestehenden Gruppe ausgewähltes Heteroatom enthalten kann, wobei das N-Atom seinerseits an eine Alkylgruppe wie CH₃, C₂H₅, C₃H₇ oder C₄H₉ oder eine Arylgruppe gebunden sein kann und das S-Atom an eine Alkyl- oder Arylgruppe gebunden oder Teil einer SO- oder SO₂-Gruppierung sein kann, und wobei die Kohlenstoffatome in der Verknüpfungsgruppe gegebenenfalls durch ein Halogenid substituiert sein können, Y¹ und Y² aus der aus Wasserstoff, Halogenid, geradkettigem C1-C20-Alkyl, verzweigtem C1-C20-Aklyl, Cycloalkyl, Aryl und Heteroaryl bestehenden Gruppe ausgewählt sind und Z für eine unsubstituierte geradkettige, verzweigte oder zyklische Alkylgruppe, eine substituierte oder unsubstituierte Arylgruppe oder eine substituierte oder unsubstituierte Heteroarylgruppe steht, wobei, wenn Z für eine substituierte Arylgruppe steht, Z für eine 2,5-disubstituierte Phenylgruppe steht,
wobei die Substituenten aus einem oder mehreren von Halogenid, Hydroxyl, C1-10-Alkoxy, CHO, CO₂H, CN, NH₂, NHR und NR₂, wobei R für C1-10-Alkyl oder Aryl steht, ausgewählt sind; und
wobei, wenn Z für eine substituierte Heteroarylgruppe steht, die Substituenten aus einem oder mehreren von Halogenid, Hydroxyl, C1-30-Alkoxy, Carboxyl, Methacryl, Vinyl, Nitril, Nitro, Sulfat, Mercapto und Amino ausgewählt sind.

13. Metallkomplex nach Anspruch 12, wobei es sich bei der Metallverbindung um eine Verbindung von Palladium (Pd), Platin (Pt), Rhodium (Rh), Iridium (Ir) oder Ruthenium (Ru) handelt.

14. Metallkomplex nach Anspruch 12 oder Anspruch 13, wobei das substituierte Paracyclophan (I) einen enantiomeren Überschuss >75% aufweist.

15. Metallkomplex nach einem der Ansprüche 12 bis 14, wobei der Metallkomplex auf einem festen Träger geträgert ist.

16. Metallkomplex, umfassend das Reaktionsprodukt einer Metallverbindung und eines substituierten Paracyclophans, bei dem es sich um:

handelt.

17. Metallkomplex nach Anspruch 16, wobei es sich bei der Metallverbindung um eine Verbindung von Palladium (Pd), Platin (Pt), Rhodium (Rh), Iridium (Ir) oder Ruthenium (Ru) handelt.

18. Metallkomplex nach Anspruch 16 oder Anspruch 17, wobei das substituierte Paracyclophan (I) einen enantiomeren Überschuss >75% aufweist.

19. Metallkomplex nach einem der Ansprüche 16 bis 18, wobei der Metallkomplex auf einem festen Träger geträgert ist.

20. Verwendung eines Metallkomplexes nach einem der Ansprüche 13 bis 15 und 17 bis 19 als Katalysator bei einer asymmetrischen Hydrierungsreaktion.

21. Verwendung eines Metallkomplexes nach einem der Ansprüche 13 bis 15 und 17 bis 19 als Katalysator für Reaktionen ausgewählt aus der Liste bestehend aus Kohlenstoff-Kohlenstoff-Kupplungsreaktionen, der enantioselektiven Isomerisierung von Olefinen, asymmetrischen Hydroborierungsreaktionen, der asymmetrischen Cyclisierung olefinischer Aldehyde, asymmetrischen Arylierungs- und Alkylierungsreaktionen und der Aminierung von Arylhalogeniden (Hartwig-Buchwald-Reaktion).

Revendications

1. Paracyclophane substitué de formule (I)

où chacun des radicaux X¹ et X² représente un groupement linéaire, ramifié ou cyclique où la liaison est formée via 2, 3 ou 4 atomes de carbone, et où la liaison comporte éventuellement en plus des atomes de carbone un hétéroatome choisi dans le groupe constitué par 0, N ou S, où l'atome N peut à son tour être lié à un groupement alkyle tel que CH₃, C₂H₅, C₃H₇ ou C₄H₉ ou un groupement aryle, et l'atome S peut être lié à un groupement alkyle ou aryle ou faire partie d'une entité SO ou SO₂ et où les atomes de carbone du groupement de liaison sont éventuellement substitués par un halogénure,
chacun des radicaux Y¹ et Y² est choisi dans le groupe constitué par l'atome d'hydrogène et les groupements halogénure, alkyle à chaîne linéaire en C1-C20, alkyle à chaîne ramifiée en C1-C20, cycloalkyle, aryle ou hétéroaryle et Z représente un groupement alkyle non substitué linéaire, ramifié ou cyclique, un groupement aryle substitué ou non substitué ou un groupement hétéroaryle substitué ou non substitué,
où, lorsque Z représente un groupement aryle substitué, Z représente un groupement phényle 2,5-disubstitué, où les substituants sont choisis parmi un ou plusieurs des membres du groupe constitué par les groupements halogénure, hydroxyle, alkoxy en C1-10, CHO, CO₂H, CN, NH₂, NHR ou NR₂ où R représente un groupement alkyle en C1-10 ou aryle ; et
où, lorsque Z représente un groupement hétéroaryle substitué, les substituants sont choisis parmi un ou plusieurs des membres du groupe constitué par les groupements halogénure, hydroxyle, alkoxy en C1-30, carboxyle, méthacryle, vinyle, nitrile, nitro, sulfate, mercapto ou amino.

2. Paracyclophane substitué selon la revendication 1, où les radicaux X¹ et X² représentent tous deux -C₂H₄-.

3. Paracyclophane substitué selon la revendication 1 ou la revendication 2, où Z représente un groupement non substitué phényle, naphtyle ou anthracyle.

4. Paracyclophane substitué selon la revendication 1 ou la revendication 2, où Z représente un groupement phényle 2,5-disubstitué.

5. Paracyclophane substitué qui est le :

6. Procédé de synthèse d'un paracyclophane substitué de formule (I) par

(a) mise en oeuvre d'une réaction de substitution sur un pseudo-orthodibromoparacyclophane pour former un bromoparacyclophane intermédiaire substitué de formule (II), et

(b) réaction du bromoparacyclophane substitué avec un composé phosphoré comprenant P(Y¹Y²),
où chacun des radicaux X¹ et X² représente un groupement linéaire, ramifié ou cyclique où la liaison est formée via 2, 3 ou 4 atomes de carbone, et où la liaison comporte éventuellement en plus des atomes de carbone un hétéroatome choisi dans le groupe constitué par 0, N ou S, où l'atome N peut à son tour être lié à un groupement alkyle tel que CH₃, C₂H₅, C₃H₇ ou C₄H₉ ou un groupement aryle, et l'atome S peut être lié à un groupement alkyle ou aryle ou faire partie d'une entité SO ou SO₂ et où les atomes de carbone du groupement de liaison sont éventuellement substitués par un halogénure,
chacun des radicaux Y¹ et Y² est choisi dans le groupe constitué par l'atome d'hydrogène et les groupements halogénure, alkyle à chaîne linéaire en C1-C20, alkyle à chaîne ramifiée en C1-C20, cycloalkyle, aryle ou hétéroaryle et Z représente un groupement alkyle substitué ou non substitué linéaire, ramifié ou cyclique, un groupement aryle substitué ou non substitué ou un groupement hétéroaryle substitué ou non substitué,
où, lorsque Z représente un groupement aryle substitué, Z représente un groupement phényle 2,5-disubstitué, où les substituants sont choisis parmi un ou plusieurs des membres du groupe constitué par les groupements halogénure, hydroxyle, alkoxy en C1-10, CHO, CO₂H, CN, NH₂, NHR ou NR₂ où R représente un groupement alkyle en C1-10 ou aryle ; et
où, lorsque Z représente un groupement alkyle substitué ou hétéroaryle substitué, les substituants sont choisis parmi un ou plusieurs des membres du groupe constitué par les groupements halogénure, hydroxyle, alkoxy en C1-30, carboxyle, méthacryle, vinyle, nitrile, nitro, sulfate, mercapto ou amino.

7. Procédé selon la revendication 6, où la réaction de substitution est mise en oeuvre en utilisant un acide boronique de formule Z-B(OH)₂, dans lequel Z peut être substitué ou non substitué.

8. Procédé selon la revendication 7, où l'acide boronique comprend un groupement phényle 2,5-disubstitué.

9. Bromoparacyclophane substitué de formule (II)

où chacun des radicaux X¹ et X² représente un groupement linéaire, ramifié ou cyclique où la liaison est formée via 2, 3 ou 4 atomes de carbone, et où la liaison comporte éventuellement en plus des atomes de carbone un hétéroatome choisi dans le groupe constitué par 0, N ou S, où l'atome N peut à son tour être lié à un groupement alkyle tel que CH₃, C₂H₅, C₃H₇ ou C₄H₉ ou un groupement aryle, et l'atome S peut être lié à un groupement alkyle ou aryle ou faire partie d'une entité SO ou SO₂ et où les atomes de carbone du groupement de liaison sont éventuellement substitués par un halogénure, et où :

a) Z représente un groupement alkyle substitué ou non substitué linéaire, ramifié ou cyclique, un groupement aryle non substitué ou un groupement hétéroaryle substitué ou non substitué,
où, lorsque Z représente un groupement alkyle substitué ou hétéroaryle substitué, les substituants sont choisis parmi un ou plusieurs des membres du groupe constitué par les groupements halogénure, hydroxyle, alkoxy en C1-30, carboxyle, méthacryle, vinyle, nitrile, nitro, sulfate, mercapto ou amino ; ou

b) Z représente un groupement phényle 2,5-disubstitué, où les substituants sont choisis parmi un ou plusieurs des membres du groupe constitué par les groupements halogénure, hydroxyle, alkoxy en C1-10, CHO, CO₂H, CN, NH₂, NHR ou NR₂ où R représente un groupement alkyle en C1-10 ou aryle.

10. Bromoparacyclophane substitué selon la revendication 9, où Z représente un groupement phényle 2,5-disubstitué.

11. Bromoparacyclophane substitué qui est le :

12. Complexe métallique comprenant le produit de réaction d'un composé métallique et d'un paracyclophane substitué de formule (I)

où chacun des radicaux X¹et X² représente un groupement linéaire, ramifié ou cyclique où la liaison est formée via 2, 3 ou 4 atomes de carbone, et où la liaison comporte éventuellement en plus des atomes de carbone un hétéroatome choisi dans le groupe constitué par 0, N ou S, où l'atome N peut à son tour être lié à un groupement alkyle tel que CH₃, C₂H₅, C₃H₇ ou C₄H₉ ou un groupement aryle, et l'atome S peut être lié à un groupement alkyle ou aryle ou faire partie d'une entité SO ou SO₂ et où les atomes de carbone du groupement de liaison sont éventuellement substitués par un halogénure,
chacun des radicaux Y¹ et Y² est choisi dans le groupe constitué par l'atome d'hydrogène et les groupements halogénure, alkyle à chaîne linéaire en C1-C20, alkyle à chaîne ramifiée en C1-C20, cycloalkyle, aryle ou hétéroaryle et Z représente un groupement alkyle non substitué linéaire, ramifié ou cyclique, un groupement aryle substitué ou non substitué ou un groupement hétéroaryle substitué ou non substitué,
où, lorsque Z représente un groupement aryle substitué, Z représente un groupement phényle 2,5-disubstitué, où les substituants sont choisis parmi un ou plusieurs des membres du groupe constitué par les groupements halogénure, hydroxyle, alkoxy en C1-10, CHO, CO₂H, CN, NH₂, NHR ou NR₂ où R représente un groupement alkyle en C1-10 ou aryle ; et
où, lorsque Z représente un groupement hétéroaryle substitué, les substituants sont choisis parmi un ou plusieurs des membres du groupe constitué par les groupements halogénure, hydroxyle, alkoxy en C1-30, carboxyle, méthacryle, vinyle, nitrile, nitro, sulfate, mercapto ou amino.

13. Complexe métallique selon la revendication 12, où le composé métallique est un composé de palladium (Pd), de platine (Pt), de rhodium (Rh), d'iridium (Ir) ou de ruthénium (Ru).

14. Complexe métallique selon la revendication 12 ou la revendication 13, où le paracyclophane substitué (I) est présent en un excès énantiomérique > 75 %.

15. Complexe métallique selon l'une quelconque des revendications 12 à 14, où le complexe métallique est supporté sur un support solide.

16. Complexe métallique comprenant le produit de réaction d'un composé métallique et d'un paracyclophane substitué qui est le :

17. Complexe métallique selon la revendication 16, où le composé métallique est un composé de palladium (Pd), de platine (Pt), de rhodium (Rh), d'iridium (Ir) ou de ruthénium (Ru).

18. Complexe métallique selon la revendication 16 ou la revendication 17, où le paracyclophane substitué (I) est présent en un excès énantiomérique > 75 %.

19. Complexe métallique selon l'une quelconque des revendications 16 à 18, où le complexe métallique est supporté sur un support solide.

20. Utilisation d'un complexe métallique selon l'une quelconque des revendications 13 à 15 et 17 à 19 en tant que catalyseur dans une réaction d'hydrogénation asymétrique.

21. Utilisation d'un complexe métallique selon l'une quelconque des revendications 13 à 15 et 17 à 19 en tant que catalyseur de réactions choisies dans la liste constituée par les réactions de couplage carbone-carbone, l'isomérisation énantiosélective d'oléfines, les réactions d'hydroboration asymétrique, la cyclisation asymétrique d'aldéhydes oléfiniques, les réactions d'arylation et d'alkylation asymétriques et l'amination d'halogénures d'aryle (réaction de Hartwig-Buchwald).